Critical Care Bulletin: August 2025

 

Immunosuppressive therapy management during sepsis in kidney transplant recipients: a prospective multicenter study

Annals of Intensive Care volume 15, Article number: 116, Published: 10 August 2025

Background

Sepsis is the leading cause of Intensive Care Unit (ICU) admissions in kidney transplant recipients (KTRs). However, the optimal immunosuppressive therapy (IST) management in this context is not well-defined. We aimed to evaluate the impact of IST management in the ICU on mortality rates and kidney graft function 6 months after inclusion in KTRs admitted for sepsis.

Methods

We conducted a multicenter, prospective, observational study over 1 year in 11 French ICUs. Inclusion criteria were all KTRs who have been transplanted for at least 3 months, admitted to the ICU for sepsis. All changes of IST (7 days prior to ICU admission or throughout the ICU stay) were collected. The primary outcome was MAKE 180 (Major Adverse Kidney Event), a composite outcome including mortality, kidney graft dysfunction and dialysis requirement at 180 days after inclusion.

Results

One hundred and twenty-four patients were included. The main cause of ICU admission was respiratory failure for 78 patients (62.9%). Predominant IST management was mycophenolic acid (MPA) discontinuation for 74 patients (59.7%) and calcineurin inhibitor (CNI) continuation for 63 patients (50.8%). By multivariable analysis, after adjustment for age, non-renal SOFA score at admission, kidney function at admission, sex, and history of cellular rejection we did not find any significant association between MAKE 180 and CNI discontinuation (adjusted OR = 1.05, 95% CI 0.87–1.26, p = 0.6). In contrast, MPA discontinuation was significantly associated with MAKE 180 (adjusted OR = 1.45, 95% CI 1.07–1.96, p = 0.018). No significant association was found between IST discontinuation and ICU-acquired infections (adjusted OR = 1.14, 95% CI 0.95–1.36, p = 0.157). Among ICU survivors, only 2 graft rejections occurred during the year following ICU discharge.

Conclusion

This study is the first prospective investigation to suggest an association between MPA discontinuation and adverse outcomes during sepsis in critically-ill KTRs. These findings must be interpreted with caution given the potential confounding introduced by SARS-Cov-2–specific treatment protocols. Further interventional trials are necessary to optimize immunosuppressive drug strategies in KTRs during sepsis.

 

Cost-effectiveness of rapid, ICU-based, syndromic PCR in hospital-acquired pneumonia: analysis of the INHALE WP3 multi-centre RCT

Critical Care volume 29, Article number: 352, Published: 08 August 2025

Background

Hospital-acquired and ventilator-associated pneumonia (HAP and VAP) are pneumonias arising > 48 h after admission or intubation respectively. Conventionally, HAP/VAP patients are given broad-spectrum empiric antibiotics at clinical diagnosis, refined after 48–72 h, once microbiology results become available. Molecular tests offer swifter results, potentially improving patient care. To investigate whether this potential is realisable, we conducted a pragmatic multi-centre RCT (‘INHALE WP3’) of rapid, syndromic polymerase chain reaction (PCR) in ICU HAP/VAP compared with standard of care. As the use of molecular tests impact on hospital resources, it is important to consider their potential value-for-money to make fully informed decisions. Consequently, INHALE WP3 included an economic evaluation, presented here. Its aim was to estimate the cost-effectiveness of an in-ICU PCR (bioMérieux BioFire FilmArray Pneumonia Panel) in HAP/VAP, informing whether to implement such technology in routine NHS care.

Methods

We collected data on patient resource use and costs. These data were combined with INHALE WP3’s two primary outcome measures: antibiotic stewardship at 24 h and clinical cure at 14 days. Cost-effectiveness analyses were carried out using regression models adjusting for site. Sensitivity analyses explored assumptions and sub-group analyses explored differential impacts.

Results

We found lower total ICU costs (including PCR costs) in the intervention (PCR-guided therapy) group. Average costs were £40,951 for standard of care compared with £33,149 for the intervention group, a difference of − £7,802 (95% CI: − £15,696, £92). For antibiotic stewardship, the PCR-guided therapy was both less costly and more effective than routine patient management. For clinical cure, we did not find PCR-guided therapy to be cost-effective due to fewer cases being cured in the intervention group.

Conclusions

We found lower average ICU costs with the Pneumonia Panel. The pneumonia panel was cost-effective in terms of antibiotic stewardship, but not clinical cure.

 

Effectiveness of targeted post-acute interventions and follow-up services for sepsis survivors: a systematic review

Critical Care volume 29, Article number: 351, Published: 08 August 2025

Background

The majority of sepsis survivors suffer from significant long-term consequences, including cognitive, psychological, and physical impairments. Despite growing recognition of these challenges, there is a lack of robust evidence regarding effective post-acute interventions to improve long-term outcomes. This systematic review aims to compile the present evidence on the effectiveness of post-acute interventions and follow-up services on patient-relevant long-term outcomes of sepsis survivors.

Methods

PubMed, Web of Science and ClinicalTrials.gov were searched for relevant publications from 01/2013 until 08/2024. Studies evaluating the effect of targeted post-acute interventions and follow-up services compared to usual care were included. Risk of bias was assessed using the RoB2- and ROBINS-I tool.

Results

Fourteen studies including 383,680 patients from high-income-countries were identified. All included studies showed either a moderate risk of bias (non-randomized studies) or some concerns (randomized trials), primarily due to residual confounding, suboptimal blinding and outcome assessment. Interventions varied substantially in terms of measures, implementation time and outcomes addressed. Rehabilitation interventions were associated with long-term survival benefits until 10 years after sepsis according to three observational studies. Additionally, one randomized controlled trial with minimization found that an 8-week exercise-based intervention improved the anaerobic threshold in sepsis survivors. Interventions (n = 7) targeting care coordination and follow-up bundles led to reductions in rehospitalization rates and mortality until 12 months post-discharge and were associated with improvements in long-term physical function and PTSD symptoms. An ICU-specific virtual reality-based intervention may reduce symptoms of PTSD and depression up to six months after exposure.

Conclusion

Post-acute interventions, such as care coordination, bundle approaches, and rehabilitation can improve patient-relevant outcomes in sepsis survivors. However, the overall number of existing studies is small, all studies may be affected by certain forms of bias and for some domains of post-sepsis impairment no specific interventions have yet been identified. Therefore, further high-quality prospective follow-up studies are needed to strengthen the evidence regarding the effectiveness and acceptability of interventions across all domains of post-sepsis impairments, particularly cognitive impairments.

 

Renal perfusion pressure: role and implications in critical illness

Annals of Intensive Care volume 15, Article number: 115, Published: 08 August 2025

Abstract

The pressure-flow relationship is fundamental to circulatory hemodynamics of any organ. In the kidney, renal perfusion pressure (RPP), defined as the gradient between mean arterial pressure and renal venous pressure or mean systemic filling pressure, serves as the principal driving pressure for renal blood flow (RBF). This concept recognizes that both arterial hypotension and venous congestion can reduce the pressure gradient for renal perfusion, potentially contributing to renal dysfunction or acute kidney injury (AKI). In health, whenever RPP fluctuates, the kidney autoregulates intrarenal vascular resistance to maintain stable RBF and glomerular filtration rate over a range of RPP. However, in critical illness, autoregulatory capacity may be impaired, and the degree of impairment can vary not only between patients but also within the same patient depending on the disease context or stage of illness. Therefore, during critical illness, inadequate RPP tends to overwhelm renal autoregulation capacity earlier than anticipated, leading to tissue hypoperfusion and increased risk of AKI. Relying on standard blood pressure targets to optimize RPP may not account for such inter- or intra-individual variations in autoregulation. Experimental models have shown that AKI can develop without overt macrocirculatory changes, implicating microcirculatory dysfunction as an important contributor too. Dynamic, multi-modal assessment of renal perfusion may offer a more precise approach to renal protection. Additionally, the focus of research has shifted towards providing new insights into individualized perfusion targets and refining RPP-guided strategies to prevent AKI among high-risk patients in ICU. The objective of this review is to describe the role of RPP, implications of dysregulated renal perfusion, approaches to monitoring renal perfusion, and potential therapies targeting RPP on the horizon for critically ill patients.

 

Incidence, kinetics, and clinical impact of thrombocytopenia in venovenous ECMO: insights from the multicenter observational PROTECMO study

Critical Care volume 29, Article number: 349, Published: 07 August 2025

Background

Thrombocytopenia is a recognized risk factor for bleeding during extracorporeal membrane oxygenation (ECMO). This study determines the incidence, risk factors, and clinical relevance of thrombocytopenia and platelet transfusions during venovenous (VV) ECMO.

Methods

The multicenter, prospective observational PROTECMO study included 652 adult patients who received VV ECMO for respiratory failure. Thrombocytopenia was classified as mild (100–149·10⁹/L), moderate (50–99·10⁹/L), or severe (< 50·10⁹/L). Bleeding events were evaluated using a modified Bleeding Academy Research Consortium score. Cox proportional hazards and logistic regression analyses were done to identify predictors, and quantify the association between platelet counts and bleeding risk.

Results

A total of 182 patients (27.9%) had thrombocytopenia at baseline (mild in 14.7%, moderate in 8.7%, and severe in 4.4%). Thrombocytopenia during ECMO, at least once in 80.2% of patients, was mild in 21.3% of cases, moderate in 32.2%, and severe in 26.7%. A 10·10⁹/L decrease in platelet count was associated with a 3.7% (95% CI: 2.4–5.0%) increase in risk of bleeding. There was no strong evidence of nonlinear relationship within the platelet count range between 25,000 and 300,000. This relation remained consistent across all ECMO weeks. Mild thrombocytopenia increased the risk of experiencing a bleeding event by 61% (hazard ratio (HR) 1.611, 95% CI 1.230–2.109, p = 0.0005), while moderate and severe thrombocytopenia increased the risk by roughly 90% (moderate: HR 1.944 (CI 1.484–2.545), p < 0.0001; severe: HR 1.876 (CI 1.275–2.7680), p = 0.0014). The risk for thrombocytopenia < 100·10⁹/L during ECMO significantly increased with ICU days prior to ECMO start, postoperative admission, immunocompromised state, renal replacement therapy, septic shock, low hemoglobin, and circuit exchange.

Conclusions

Thrombocytopenia is highly prevalent in VV ECMO, and associated with a significant increase in the risk of bleeding, and a reduction in 6-month survival, particularly at platelet counts below 100·10⁹/L. Further research is needed to better define the outcomes associated with specific thresholds for transfusion of platelets.

 

A prediction model for ‘ICU mortality or prolonged ICU stay’ in critically unwell patients with acute pancreatitis: insights from a 2003–2020 cohort analysis using the ANZICS-CORE database

Critical Care volume 29, Article number: 347, Published: 06 August 2025

Objective

Critically unwell patients with acute pancreatitis (AP) are at increased risk of mortality and prolonged ICU length of stay (LOS). We quantified the frequency, risk factors and complications of prolonged ICU LOS in a large cohort of critically unwell adult patients with AP and developed a model to predict a low-risk trajectory ‘survived ICU with ICU LOS ≤7 days’ versus a high-risk trajectory ‘ICU mortality or ICU LOS > 7 days’.

Methods

A retrospective cohort analysis of adult patients admitted to Australian and New Zealand ICUs with AP between 2003 and 2020 was conducted using the Australian and New Zealand Intensive Care Society Centre for Outcome Reporting and Evaluation database. Data was censored to December 2020 in order to pre-date the COVID-19 pandemic. The incidence, risk factors and outcomes related to prolonged ICU LOS in AP patients was reported. Multivariate logistic regression was used to build a prediction model for a low-risk versus high-risk outcome. Discrimination was performed with 10-fold cross validation and calibration plot analysis was reported.

Main results

13,275 patients met inclusion criteria; 60% were male, with a mean age 59±18, mean APACHE III 56±26. 2860 (21.6%) had an ICU LOS > 7 days, 1022 (7.7%) died in ICU, and 3557 (26.8%) had a high-risk trajectory. Prolonged ICU LOS was associated with increased ICU mortality (OR 1.57 95% CI 1.43–1.73 p < 0.001), hospital mortality (OR 1.69 95% CI 1.56–1.83 p < 0.001), and resource use: mechanical ventilation (OR 5.99 95% CI 5.21–6.90 p < 0.001), inotrope/vasopressor support (OR 3.27 95% CI 2.82–3.79 p < 0.001) and dialysis (OR 4.12 95% CI 3.63–4.68 p < 0.001). Model accuracy was 79.5%, Cohen K = 0.49 and AUROC 0.827. For a high-risk trajectory, sensitivity was 0.54 and specificity 0.916. APACHE III, PaO2:FiO2 ratio and early mechanical ventilation were the most influential covariates. Prolonged ICU LOS was associated with increased rate of hospital discharge to rehabilitation or a nursing home.

Conclusions

More than a quarter of ICU patients with AP have a high-risk trajectory. Prolonged ICU admissions are associated with significantly worse mortality and hospital outcomes, and increase resource use. Our prediction model, if confirmed in future studies, may present an opportunity for prognostic enrichment in patients with more severe disease.

 

Beyond blood-brain barrier disruption and molecular weight: compartmental kinetics of S100B and NSE for neurological prognostication after cardiac arrest

Critical Care volume 29, Article number: 342, Published: 04 August 2025

 Background

The prognostic value of serum biomarkers after out-of-hospital cardiac arrest (OHCA) depends on timing, but the physiological basis remains unclear. We investigated whether blood–brain barrier (BBB) integrity and biomarker-specific properties explain the time-dependent differences in prognostic performance.

Methods

This retrospective study included comatose adult OHCA survivors who underwent paired serum and cerebrospinal fluid (CSF) measurements of neuron-specific enolase (NSE; 47 kDa) and S100 calcium-binding protein B (S100B; 21 kDa) at 0 (H0), 24 (H24), 48 (H48), and 72 (H72) h after return of spontaneous circulation. BBB disruption was assessed using the CSF/serum albumin quotient (Q_A). Prognostic performance was assessed using AUC analysis for 6-month poor neurological outcome (Cerebral Performance Category 3–5).

Results

Among 111 patients (59% poor outcome), 646 serum and 620 CSF samples were analyzed. BBB disruption was more severe in the poor outcome group at all timepoints (all P < 0.001), peaking at H24 (Q_A 0.0282 [IQR 0.0150–0.120]) and remaining elevated at H72 (0.0228 [IQR 0.0147–0.0598]). In the poor outcome group, serum S100B levels peaked at H0 (0.80 ng/mL [IQR 0.39–2.81]) and declined despite a persistent elevation in CSF levels at or above the upper detection limit (≥ 30 ng/mL). Conversely, NSE levels progressively increased in both compartments, with serum and CSF levels increasing in parallel over time. Serum NSE concentrations showed a time-dependent improvement in prognostic accuracy, peaking at H72 (AUC 0.88), whereas S100B concentrations maintained stable performance across all timepoints (AUCs 0.79–0.85, all P > 0.4). Notably, the prognostic performance of S100B remained relatively consistent regardless of BBB disruption severity, whereas NSE showed progressively improved predictive accuracy with increased BBB disruption. Across all timepoints, CSF biomarkers—particularly S100B and NSE—showed consistently higher AUCs than serum, suggesting superior prognostic utility.

Conclusions

Serum NSE levels closely reflect the degree of BBB disruption and CSF levels, while S100B exhibits a transient early-phase profile, with decreased serum detectability over time, even in the presence of sustained CSF elevation or severe BBB disruption. These findings highlight the importance of interpreting biomarker kinetics across compartments and timepoints rather than relying on molecular weight or BBB status alone.

 

Targeting high circulating dipeptidyl peptidase 3 in circulatory failure

Critical Care volume 29, Article number: 340, Published: 31 July 2025

Abstract

Circulating dipeptidyl peptidase 3 is a new biomarker linked to circulatory failure prognosis and pathophysiology and is a potential actionable therapeutic target. In this short review intended for the clinician, a question-and-answer format provides key insights on the nature of this biomarker and the therapeutical potential of its targeted inhibition in critically ill patients.

 

Assessing inspiratory drive and effort in critically ill patients at the bedside

Critical Care volume 29, Article number: 339, Published: 31 July 2025

Abstract

Monitoring inspiratory drive and effort may aid proper selection and setting of respiratory support in patients with acute respiratory failure (ARF), whether they are intubated or not. Although diaphragmatic electrical activity (EAdi) and esophageal manometry can be considered the reference methods for assessing respiratory drive and inspiratory effort, respectively, various alternative techniques exist, each with distinct advantages and limitations. This narrative review provides a comprehensive overview of bedside methods to assess respiratory drive and effort, with a primary focus on patients with ARF. First, EAdi and esophageal manometry are described and discussed as reference techniques. Then, alternative methods are categorized along the neuromechanical pathway from inspiratory drive to muscular effort into three groups: (1) techniques assessing the respiratory drive: airway occlusion pressure (P0.1), mean inspiratory flow (Vt/Ti) and respiratory muscle surface electromyography (sEMG); (2) techniques assessing the respiratory muscle effort: whole-breath occlusion pressure (ΔPocc), pressure-muscle index (PMI), nasal pressure swing (ΔPnose), diaphragm ultrasonography (USdi), central venous pressure swing (ΔCVP), breathing effort (BREF) models, and flow index; (3) techniques and clinical parameters assessing the consequences of effort: tidal volume (Vt), electrical impedance tomography (EIT), dyspnea. For each, we summarize the physiological rationale, measurement methodology, interpretation of results, and key limitations.

 

Physiological and clinical effects of two ultraprotective ventilation strategies in patients with veno-venous extracorporeal membrane oxygenation: the ECMOVENT study

Annals of Intensive Care volume 15, Article number: 111, Published: 01 August 2025

Purpose

The optimal ventilation strategy in acute respiratory distress syndrome (ARDS) patients with veno-venous extracorporeal membrane oxygenation (VV-ECMO) remains unknown. We aimed to compare the effects of two ultra-protective ventilatory strategies applied to patients with ARDS and VV-ECMO.

Methods

Our study was an observational, retrospective, single-center study with a before-and-after design. All consecutive patients treated with VV-ECMO for severe ARDS between 2016 and 2023 were included. Before 2021, patients received a quasi-apneic ventilation strategy in assist-controlled volume mode with a tidal volume (V_T) of 1 ml.kg⁻¹ predicted body weight (PBW), a respiratory rate (RR) of 5 min⁻¹ and a PEEP set to keep plateau pressure (P_PLAT) between 20 and 25 cmH₂O. From 2021 onwards, the protocolized ventilatory strategy consisted in pressure-controlled mode with a PEEP of 14 cmH₂O, a driving pressure (∆P) of 8 cmH₂O and a RR of 10 min⁻¹. We evaluated the impact of strategies on longitudinal respiratory mechanics and on the time to successful ECMO weaning at day-90 after VV-ECMO canulation.

Results

121 patients were enrolled, with 69 receiving the VT1 strategy, and 52 the ∆P8 strategy. Over the first 7 days of ECMO, the ∆P8 strategy was associated with significantly higher ∆P and RR, lower PaCO₂, and higher static elastic mechanical power, compared with the VT1 strategy. The day-90 survival rate was 30% with the VT1 strategy, and 42% with the ∆P8 strategy (P = 0.19). Time to successful VV-ECMO weaning was 7 [4–13] days in day-90 survivors, with no significant difference between groups. The adjusted subdistribution hazard ratio associated with the ∆P8 strategy was 0.99 (95% confidence interval: 0.53–1.84), as compared to the VT1 strategy (P > 0.9).

Conclusions

In the context of our center, a ventilatory strategy targeting a PEEP of 14 cmH₂O, a ∆P of 8 cmH₂O and a RR of 10 min⁻¹ led to the application of ∆P, RR and static elastic mechanical power and improved decarboxylation, compared to a strategy in volumetric mode with a V_T of 1 ml.kg⁻¹ PBW and a RR of 5 min⁻¹, in patients with ARDS and VV-ECMO. No significant difference on clinical outcomes was observed between both strategies.

 

Vasopressin and its analogues in patients with septic shock: holy Grail or unfulfilled promise?

Critical Care volume 29, Article number: 333, Published: 29 July 2025

Abstract

The Surviving Sepsis Campaign (SSC) recommends norepinephrine as first-line vasopressor in patients with septic shock. For many years, there has been growing evidence that high doses of norepinephrine might have cardiac and immunological adverse effects and be associated with poorer outcomes. Current SSC guidelines therefore suggest adding vasopressin, a non-catecholaminergic vasopressor, as a second-line vasopressor rather than increasing the norepinephrine dose in patients requiring doses of norepinephrine base > 0.25–0.50 µg/kg/min, after excluding persistent hypovolemia and cardiac dysfunction. Vasopressin is a peptide hormone that causes vasoconstriction through its specific receptor, the arginine vasopressin receptor V1. Up to one-third of patients with septic shock may have vasopressin deficiency, which contributes to refractory septic shock. Vasopressin use is associated with a norepinephrine-sparing effect, which may in turn reduce the complications induced by high-doses of norepinephrine, by decreasing the vasopressor load: this is the concept of decatecholaminization. Nevertheless, the use of vasopressin in patients with septic shock has not yet demonstrated clear benefits in terms of patient outcomes, such as less cardiotoxicity, reduced use of renal replacement therapy or decreased mortality. The heterogeneity in the use of vasopressin and the definition of early vasopressin administration between different studies as well as many unresolved issues regarding the use of vasopressin in patients with septic shock could explain the absence of clear and relevant clinical benefits. Thus, the identification of subgroups of patients likely to benefit the most from vasopressin, the management of vasopressin administration (time to initiation, optimal doses, weaning strategy) and a better understanding of the interactions between vasopressin and corticosteroids represent major areas of research for future studies.

 

Candida auris infections in ICU patients: risk factors, outcomes, and antifungal resistance patterns

Critical Care volume 29, Article number: 332, Published: 28 July 2025

Background

Candida auris has emerged as a major nosocomial pathogen in intensive care units worldwide due to its multidrug resistance, environmental persistence, and high transmission potential. While several outbreak reports exist, there remains limited comparative data on clinical features, resistance profiles, and outcomes between Candida auris and non-auris Candida candidemia, particularly in Indian ICU settings. This study aimed to evaluate the incidence, risk factors, antifungal resistance, and clinical outcomes of Candida auris bloodstream infections in comparison to non-auris Candida infections among ICU patients.

Methods

This retrospective cohort study was conducted over four years (January 2020–December 2023) in the ICU of a tertiary care hospital in eastern India. Adult patients (≥ 18 years) with culture-confirmed candidemia were included and stratified into Candida auris and non-auris groups. Demographic, clinical, therapeutic, and microbiological data were extracted. Antifungal susceptibility testing was performed as per CLSI and CDC guidelines. Multivariate logistic regression identified risk factors associated with Candida auris infection. Survival analysis were compared using Kaplan–Meier and Cox regression analysis.

Results

Of 267 ICU patients with candidemia, 38 (14.2%) had Candida auris infection. Candida auris patients were older (median age 60 vs. 53 years) and had lower SOFA scores at admission (median 7 vs. 8; p = 0.02). On multivariate analysis, increasing age (OR 1.10, p = 0.0003) and female sex (OR 16.35, p = 0.012) were independently associated with Candida auris infection. Fluconazole resistance was 94.7% in Candida auris isolates, with amphotericin B and echinocandin resistance in 39.5% and 7.9%, respectively. ICU mortality did not differ significantly between Candida auris and non-auris groups (31.6% vs. 34.5%; p = 0.854), and survival analysis showed no statistically significant difference (log-rank p = 0.07).

Conclusion

This study highlights the growing burden of Candida auris in intensive care unit settings, demonstrating a substantial incidence without increased mortality compared to non-auris Candida species. Advancing age and female sex emerged as significant independent risk factors, emphasizing the need for continued surveillance and targeted risk assessment in regions where Candida auris is endemic.

 

 

 

The impact of intensive care strain on patients’ outcomes—a multinational observational cohort (UNITE-COVID) study

Critical Care volume 29, Article number: 329, Published: 28 July 2025

Abstract

Purpose

Intensive care unit (ICU) strain is associated with increased mortality. Most strain metrics focus on ‘simple’ measures such as bed occupancy or admission rates. There is limited data on mitigation strategies, such as procedure teams or staff well-being services on strain, or the impact of increased patient-to-nurse ratios and non-ICU trained nurses working in ICU.

Methods

Using the multi-national UNITE-COVID study, collecting data from ICUs on their day of peak bed occupancy in two periods (2020 and 2021) of the COVID-19 pandemic, we evaluated metrics of strain (Bed occupancy, patient: nurse ratio, use of non-ICU staff and shortages of consumables) and potential mitigators (procedural support teams and staff well-being interventions). We examined how these related to outcomes (mortality, complications, length of stay).

Results

In both epochs, ICUs experienced significant strain, with ICU bed expansion to 133% and 163% respectively, whilst patient-to-nurse ratios increased by 0.4 and 0.3. Consumable shortages were widespread in 2020. Mortality was inversely correlated with staff well-being interventions in both epochs. Complications were inversely correlated with procedure support teams, and positively correlated with staffing ratios. In regression models, pressure sores were reduced in presence of support teams (p = 0.004) and increased with increasing patients per nurse (p = 0.05) whilst unplanned extubations were related to non-ICU trained staff working in ICU(p = 0.02).

Conclusions

COVID-19 induced ICU strain had effects beyond mortality, including increases in complications. Staff pressure and lack of ICU training were related to specific complications, whilst support teams and well-being interventions were associated with improved outcomes.

 

Oral care for intubated patients in the intensive care unit: examination of bacterial count and microbiota

Critical Care volume 29, Article number: 320, Published: 23 July 2025

Abstract

Background

Ventilator-associated pneumonia (VAP) after tracheal intubation is a major infectious complication in patients in the intensive care unit (ICU), with an incidence of 8–28%. Oral care in the ICU is essential; however, the presence of an intubation tube and restricted mouth opening cause complications. A healthy commensal microflora in the oral cavity resists colonization by respiratory pathogens, and poor oral hygiene may increase the risk for VAP. In this study, we examined the effectiveness of oral care on oral bacterial counts and microbial diversity in patients admitted to the ICU.

Methods

Fifteen ICU patients were included in this study. Oral microbiome samples were collected by swabbing the surface of the tongue. Oral bacterial counts were measured at four time points: before and after oral care, both pre- and post-extubation. Additionally, microbiome analysis was conducted twice: once before oral care pre-extubation, and once before oral care post-extubation. Oral bacterial counts were assessed using a bacterial counter, and microbiome analysis was performed through 16S rRNA gene amplicon sequencing.

Results

Oral bacterial counts significantly decreased after oral care at both pre- and post-extubation time points. Microbiome analysis revealed significant differences in alpha diversity pre- and post-extubation samples. Samples post extubation were less diverse.

Conclusions

This study demonstrates that oral care effectively reduces bacterial counts in ICU patients, both pre- and post-extubation. Microbiome analysis revealed shifts in microbial diversity, suggesting that the oral microbiota was disrupted during intubation. Given the risk of VAP, oral care may play an important role to prevent VAP in ICU settings.

 

Awareness, knowledge and practices related to intra-abdominal hypertension and abdominal compartment syndrome among intensive care providers: a systematic scoping review

Annals of Intensive Care volume 15, Article number: 106, Published: 24 July 2025

Abstract

Objectives

To provide a comprehensive overview of current research on intensive care providers’ awareness, knowledge, and practices regarding IAP/IAH/ACS, as well as barriers to IAP measurement.

Methods

This scoping review was guided by the framework of Arksey and Malley. Eight databases were searched to identify research published after 2007, including MEDLINE Complete, EMBASE, Web of Science, Cochrane Library, CINAHL Complete, ProQuest Health & Medical Complete, CNKI, and WANFANG. Two researchers reviewed and screened potentially relevant studies based on title and abstract. Full-text articles were independently assessed for eligibility based on predefined inclusion criteria.

Results

Nineteen articles were included. Overall, pediatric intensive care providers demonstrated a lower awareness and knowledge of IAH/ACS compared to adult intensive care providers, particularly regarding the consensus definitions of IAH/ACS in critically ill children. IAP measurement has not been adequately integrated into clinical practice, with 18.0–73.0% of intensive care providers reporting they have never measured it. The frequency of IAP measurements and the criteria for determining which patients necessitate such measurements exhibited significant variability across different hospitals. The most frequently mentioned barriers to IAP measurement include a lack of knowledge regarding IAP measurement among adult intensivists, an overreliance on physical examination among pediatric intensivists, uncertainty in interpreting IAP data among adult intensive care nurses, and challenges in identifying populations at high risk of IAH among pediatric intensive care nurses. Diuretics were mentioned most often in the management of IAH/ACS, followed by administration of vasopressors and inotropes, decompressive laparotomy, and judicious administration of fluids and blood products. 37.0–66.3% of adult intensivists would choose a decompressive laparotomy in cases of ACS, whereas pediatric intensivists were less inclined to opt for the same approach.

Conclusions

Since the publication of the WSACS consensus in 2007, there has been an improvement in awareness and knowledge regarding IAP/IAH/ACS among intensive care providers. Nevertheless, the understanding of the consensus definitions regarding IAH/ACS remains inadequate, particularly among pediatric intensive care providers. It is imperative to advocate for the implementation of WSACS guidelines in hospitals through targeted training programs and to promote the routine practice of IAP measurement in clinical settings.

 

Return on investment of rapid ICU workforce upskilling: an economic and cost-effectiveness analysis

Intensive Care Medicine: Volume 51, pages 1453–1461, Published: 21 July 2025

Abstract

Purpose

Although healthcare crises are infrequent, they may place extraordinary stress on Intensive Care Units (ICUs), often exposing critical weaknesses in workforce planning and resulting in acute staffing shortages. This study presents a comprehensive economic evaluation of large-scale, rapid ICU workforce upskilling as a strategic response to such pressures. Specifically, we assess the cost-effectiveness, economic sustainability, and resilience-building potential of these interventions during crisis conditions.

Methods

C19_SPACE, a Europe-wide upskilling initiative led by the European Society of Intensive Care Medicine (ESICM), was implemented across 24 countries between 2020 and 2021. A societal economic evaluation and return on investment (ROI) was calculated through deterministic modeling and validated using probabilistic sensitivity analysis across a range of plausible scenarios, including variations in patient throughput, training efficacy, and healthcare system parameters.

Results

The total societal investment in the program was €20.1 million, translating to an average cost of €1146 per participant and €1720 per Quality-Adjusted Healthcare Worker (QAHW). Deterministic modeling estimated an ROI of 478%, with program costs fully recovered in just 5.1 days. Probabilistic sensitivity analysis confirmed the robustness of these findings, with a mean ROI of 455% (95% CI 130–1029%) and a median break-even point of 5.4 days (95% CI 2.66–13.04 days).

Conclusion

Rapid, structured ICU workforce upskilling initiatives deliver substantial economic returns and significantly expands healthcare capacity. Strategic investment in emergency workforce upskilling is economically sound and crucial for healthcare system resilience during future crises.

Critical Care Bulletin: July 2025

 

Association of hospital-level continuous kidney replacement therapy use and mortality in critically ill patients with acute kidney injury

Intensive Care Medicine, Published: 30 June 2025

Purpose

In numerous high-risk medical and surgical conditions, an increased volume of patients and procedures is associated with improved processes and survival. This study examined the association of hospital-level continuous kidney replacement therapy (CKRT) utilization rates with all-cause hospital mortality in critically ill patients with acute kidney injury (AKI).

Methods

This multicenter cohort study used data from patients admitted to the intensive care unit (ICU) within the Premier Incorporated AI (PINC-AI) database. Patients were critically ill adults with AKI receiving kidney replacement therapy (KRT) in U.S. hospitals that offered both CKRT and intermittent hemodialysis. Hospitals were characterized according to their CKRT utilization in the ICU, and risk-adjusted association with all-cause hospital mortality by day 90 was estimated.

Results

Among 49,685 patients with AKI admitted to 426 acute care U.S. hospitals and treated with KRT in the ICU, a higher hospital-level CKRT utilization rate was associated with lower patient-level risk-adjusted hospital mortality. Hospitals with higher CKRT utilization rates (CKRT use in ≥ 31.5% of KRT patients per year) had a 15% lower adjusted probability of death compared with hospitals with lower CKRT utilization rates (CKRT use in < 8% of KRT patients per year). When compared with the first quartile of hospital-level CKRT use, the third (adjusted hazard ratio [aHR], 0.93, 95%CI: 0.89–0.98) and fourth (aHR, 0.85, 95%CI: 0.81–0.89) quartiles were associated with lower risk-adjusted hospital mortality. Findings were consistent in several sensitivity analyses.

Conclusions

Among critically ill adults with AKI requiring KRT, treatment in hospitals with higher CKRT utilization rates was associated with reduced hospital mortality.

 

Short- and long-term outcomes and 15-year time trends of kidney replacement therapy in critically ill patients with obesity: an observational cohort

Intensive Care Medicine, Published: 30 June 2025

Purpose

Obesity is a public health challenge and a risk factor for chronic and acute kidney injury (AKI). The impact of kidney replacement therapy (KRT) on mortality in this specific population remains unclear. The objectives of this study were to evaluate the association between KRT and short- and long-term outcomes in patients with obesity, and to analyze trends over time in mortality as well as AKI and KRT incidence.

Methods

A retrospective analysis was conducted on all consecutive patients with obesity (body mass index ≥ 30 kg/m²) admitted to a medico-surgical intensive care unit from 2009 to 2024. AKI was defined using KDIGO criteria. The primary outcome was 90-day mortality assessed with Kaplan–Meier curves and multivariate Cox analysis. Secondary outcomes included 1-year mortality and time trends assessed on 90-day mortality, AKI, and KRT incidence, as well as SAPS II score.

Results

Among 2,192 patients with obesity included in the study, 295 (13.5%) required KRT. The 90-day mortality was significantly higher in the KRT group compared to the non-KRT group (49.8% (95% CI [44.1–55.5] vs. 18.9% (95% CI [17.2–20.7]), p < 0.0001). Multivariate analysis confirmed that KRT was independently associated with increased mortality. Over the 15-year period, AKI incidence decreased (p < 0.001).

Conclusion

Among critically ill obese patients, KRT was independently associated with increased 90-day mortality. These results highlight the need for prospective studies to better define optimal management strategies in this high-risk population.

 

Self-reported symptoms in ICU patients and their impact on long-term outcomes—a prospective multicenter study

Intensive Care Medicine, Published: 30 June 2025

Purpose

The aim was to identify possible associations between patient symptom subgroups, identified while in the ICU, adjusted for clinical and demographic variables and PICS outcomes, three months after ICU admission.

Methods

A prospective multi-center cohort study. Based on reported symptom prevalence in the ICU, patients were categorized into a Low, Middle or High symptom subgroup. PICS outcomes were measured using validated questionnaires (i.e., Katz Index; Cognitive Failure questionnaire, The Hospital Anxiety and Depression Scale, Impact of Event Scale) three months after ICU admission. Possible associations between ICU symptom subgroups and dichotomized PICS outcomes were modeled using conditional backward logistic regression.

Results

We included 175 patients with a median age of 62 years (interquartile range 49–70) and 65.1% were males. Three months after ICU admission, 23.5% had physical disability, 12.1% cognitive failure, 18.3% anxiety, 16.6% depression, and 16.7% post-traumatic stress. In multivariate analyses, patients in the High symptom subgroup compared to Low/Middle symptom subgroups had higher odds for worse outcomes in all PICS domains. The odds ratios (95%CI) were 3.31 (1.25–8.78) for physical disability, 3.56 (1.20–10.60) for cognitive failure, 3.70 (1.41–9.67) for anxiety, 4.74 (1.79–12.58) for depression and 4.38 (1.49–12.84) for post-traumatic stress, respectively.

Conclusion

A subgroup of patients with high symptom burden during ICU stay had worse physical, cognitive and mental health outcomes three months after ICU admission compared to patients with medium/low symptom burden. Future studies are needed to evaluate if early interventions in the ICU can reduce long-time burden in the PICS domains in ICU survivors.

 

Prognosis of Nonagenarian ICU Patients A Bayesian analysis of prospective European studies

Annals of Intensive Care volume 15, Article number: 85 (2025)

Background

As the population ages, the number of very elderly patients (≥ 90 years, nonagenarians) admitted to intensive care units (ICUs) is increasing. This trend raises concerns about the appropriateness of ICU care for this age group, especially due to the uncertainty surrounding their prognosis. Some studies suggest that elderly ICU patients have outcomes similar to slightly younger patients, but skepticism remains due to clinical judgment, cultural attitudes, and resource allocation concerns.

Methods

We reassessed the 30-day mortality risk of nonagenarians admitted to ICUs using data from the VIP1, VIP2, and COVIP registries. Bayesian statistical methods, including Markov Chain Monte Carlo (MCMC) simulations, were used to estimate the relative risk (RR) of mortality for nonagenarians compared to octogenarians (80–89 years). Various prior assumptions (non-informative, pessimistic, and skeptical) were incorporated. The analysis adjusted for key variables such as SOFA score, frailty, and treatment limitations.

Results

A total of 8,408 patients were included, consisting of 807 nonagenarians and 7,601 octogenarians. The 30-day mortality rate was 45% for nonagenarians and 42% for octogenarians (p = 0.12). Bayesian analysis revealed a high probability (81.1–97.9%) that nonagenarians face a higher 30-day mortality risk. However, the probability of a clinically significantly increase in mortality (RR > 1.1) was moderate (28.9–34.7%), and the probability of a substantial increase (RR > 1.2) was very low (0.03–1.9%).

Conclusion

Nonagenarians in the ICU have a slightly higher 30-day mortality risk compared to octogenarians, but the increase is unlikely to exceed clinically meaningful thresholds. Bayesian methods offer more refined mortality risk assessment, suggesting that ICU admission decisions should be based on individualized factors, not just age.

 

Impact of awake prone positioning duration on intubation or mortality in COVID-19 patients with acute respiratory failure: secondary analysis of a randomized clinical trial

Annals of Intensive Care volume 15, Article number: 84 (2025)

Background

Compared with shorter awake prone positioning (APP), prolonged APP (≥ 12 h daily) reduces the intubation rate in patients with COVID-19-related acute hypoxemic respiratory failure (AHRF). However, the optimal APP duration is uncertain. In this secondary analysis, we aimed to explore whether a longer APP duration is associated with improved outcomes and to identify the optimal duration of APP.

Methods

Data from a multicenter randomized controlled trial involving nonintubated COVID-19 patients with AHRF were analyzed. Daily APP duration over 7 days after randomization was recorded as the primary exposure in present study. The primary outcome was the time from randomization to APP failure, which was defined as a composite of tracheal intubation or mortality within 28 days. A Cox proportional hazards regression model was employed to elucidate the associations, and the daily duration of APP was treated as time dependent.

Results

A total of 409 patients were randomized in the original trial, and 408 were enrolled in this analysis. Among these patients, 105 (25.7%) experienced APP failure. A longer daily APP duration was associated with a lower risk of APP failure, with a hazard ratio (HR) of 0.93 (95% confidence interval (CI): 0.88–0.98), and the association was significant only during the first three days after randomization. There was a nonlinear relationship between the daily APP duration and the risk of APP failure (P = 0.015 for nonlinearity). Compared with patients whose APP duration ranged from 8 to 12 h per day, patients with less than 8 h of APP per day had a greater risk of APP failure (HR 2.44, 95% CI 1.21–4.92), whereas extending APP beyond 12 h per day did not improve the outcomes further (HR 1.03, 95% CI 0.51–2.10, P = 0.932).

Interpretation

A longer daily APP duration was associated with a reduced risk of APP failure in COVID-19-related AHRF patients, and the optimal APP duration was 8–12 h per day.

Clinical trial ClinicalTrials.gov: NCT05677984, Registered January 3, 2023. https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000CST9&selectaction=Edit&uid=U0000YKY&ts=4&cx=-x0muek

 

 

The effects of extracorporeal blood purification (oXiris®) in patients with cardiogenic shock who require VA-ECMO (CLEAN ECMO): a prospective, open-label, randomized controlled pilot study

Critical Care volume 29, Article number: 255 (2025)

Background

A systemic inflammatory response can contribute to poor outcomes in an advanced stage of cardiogenic shock (CS). We investigated the efficacy of extracorporeal endotoxin and cytokine adsorption using oXiris in patients with CS undergoing venoarterial extracorporeal membrane oxygenation (VA-ECMO).

Methods

In this prospective, single-center, randomized, open-label pilot trial, 40 patients with CS who were undergoing VA-ECMO were randomly assigned to receive either oXiris for 24 h (n = 20) or usual care (n = 20). The primary endpoint was endotoxin levels at 48 h. Secondary endpoints included changes in inflammatory cytokines, vasoactive-inotropic score (VIS), ECMO weaning success, and in-hospital and 30-day mortality.

Results

The median endotoxin levels at 48 h were 0.5 (IQR 0.4–1.0) in the oXiris group and 0.4 (IQR 0.2–0.5) in the control group, with no significant difference between them (P = 0.097). The oXiris group showed significant temporal reductions in GDF-15 and IL-6 levels, with IL-6 revealing significant reductions from baseline to 24 h (P = 0.020) and from baseline to 7 days (P = 0.003). VIS decreased significantly from baseline to 48 h (-13.63, 95% CI: -20.90 – -6.34, P < 0.001) and 7 days (-12.19, 95% CI: -21.0 – -3.31, P = 0.007) in the oXiris group, but intergroup differences were insignificant. ECMO weaning success, duration of ECMO support, and mortality rates were similar between the groups.

Conclusion

In this pilot study conducted on CS patients requiring VA-ECMO, oXiris treatment did not significantly reduce endotoxin levels or improve patient centered clinical outcomes.

 

Can we predict the future of respiratory failure prediction?

Critical Care volume 29, Article number: 253 (2025)

Background

Mortality in patients with acute respiratory failure remains high. Predicting progression of acute respiratory failure may be critical to improving patient outcomes. Machine learning, a subset of artificial intelligence is a rapidly expanding area, which is being integrated into several areas of clinical medicine. This manuscript will address the knowledge gap in predicting the onset and progression of respiratory failure, provide a review of existing prognostic strategies, and provide a clinical perspective on the implementation and future integration of machine learning into clinical care.

Main body

Existing strategies for predicting respiratory failure, such as prediction scores and biomarkers, offer both strengths and limitations. While these tools provide some prognostic value, machine learning presents a promising, data-driven approach to prognostication in the intensive care unit. Machine learning has already shown success in various areas of clinical medicine, although relatively few algorithms target respiratory failure prediction specifically. As machine learning grows in the context of respiratory failure, outcomes such as the need for invasive mechanical ventilation and escalation of respiratory support (e.g. non-invasive ventilation) have been identified as key targets. However, the development and implementation of machine learning models in clinical care involves complex challenges. Future success will depend on rigorous model validation, clinician collaboration, thoughtful trial design, and the application of implementation science to ensure integration into clinical care.

Conclusion

Machine learning holds promise for optimizing treatment strategies and potentially improving outcomes in respiratory failure. However, further research and development are necessary to fully realize its potential in clinical practice.

 

What is the optimal approach to analyse ventilator-free days? A simulation study

Critical Care volume 29, Article number: 251 (2025)

Background

Ventilator-free days (VFDs) are a composite outcome in critical care research, reflecting both survival and mechanical ventilation duration. However, analysis methods for VFDs are inconsistent, with some focusing on counts and others on time-to-event outcomes, while other approaches such as the multistate model and the win ratio have emerged. We aimed to evaluate various statistical models through simulations to identify the optimal approach for analysing VFDs.

Methods

First, 16 datasets of 300 individuals were simulated, comparing a control group to an intervention with varying survival rates and ventilation durations. Various statistical models were evaluated for statistical power and Type I error rate. Four clinical trial datasets (LIVE study, NCT02149589; ARMA study, NCT00000579; ACURASYS study, NCT00299650; COVIDICUS study, NCT04344730) were then used to apply the same statistical models to analyse VFDs. Twelve statistical methods were evaluated, including count-based, time-to-event approaches, and the win-ratio. Additionally, sensitivity analyses were conducted.

Results

Most statistical methods effectively controlled Type I error rate, except for the zero-inflated and hurdle Poisson/negative binomial count submodels, as well as the cause-specific Cox regression model for death. The power to detect survival benefit and ventilation duration effects varied, with time-to-event approaches, the Mann–Whitney test, the proportional odds model and the win ratio generally performing best. Similar results were observed in sensitivity analyses. In the real datasets, the multistate model, the Mann–Whitney test, the proportional odds model and the win ratio generally showed a significant association between VFDs and randomisation groups.

Conclusions

The multistate model could be recommended as the optimal approach for analysing VFDs, as it outperformed the other methods and offers a more interpretable effect size than the proportional odds model and the win ratio.

 

Can we reliably use pulse pressure as a surrogate for stroke volume? Physiological background and potential clinical implications for shock resuscitation

Critical Care volume 29, Article number: 249 (2025)

Abstract

In critically ill patients, early hemodynamic assessment is essential for guiding shock resuscitation. While cardiac output (CO) is a key indicator of circulatory status, its measurement is often limited by technical and practical constraints. This perspective explores the physiological and clinical relevance of pulse pressure (PP) as a potential surrogate for stroke volume (SV), emphasizing its accessibility at the bedside. The paper discusses how factors such as arterial compliance, vascular tone, and pulse wave amplification influence the PP-SV relationship, often complicating interpretation in acute and complex hemodynamic states. It also examines the effects of vasopressors, vascular decoupling, and catheter site on PP measurements, particularly in septic shock. Despite its limitations, the review highlights how peripheral PP, when carefully interpreted, may aid in identifying low SV and guiding early resuscitation strategies.

 

Muscle weakness after critical illness: unravelling biological mechanisms and clinical hurdles

Critical Care volume 29, Article number: 248 (2025)

Abstract

Survivors of intensive care unit (ICU) are increasingly numerous because of better hospital care. However, several consequences of an ICU stay, known as post-intensive care syndrome, worsen long-term prognoses. A predominant feature in survivors is reduced muscle strength, mass, and physical function. This leads to lower exercise capacity, long-lasting physical disability, higher mortality risk, and subsequent health costs. While ICU-acquired muscle weakness has been extensively studied these past decades, underlying mechanisms of post-ICU muscle weakness remain poorly understood, and there is still no evidence-based treatment for improving long-term physical outcomes. One hypothesis, among others, could be that the pathophysiology is dynamic over time, differing between the acute ICU and post-ICU recovery periods. This narrative review aims to address the clinical, physiological and biological determinants of persistent muscle dysfunction in ICU survivors, with particular attention to the molecular, cellular and systemic mechanisms involved. Specifically, pre-ICU health factors such as obesity and sarcopenia, ICU-related complications and treatments, and post-ICU management all influence recovery. Dysfunctions in the neuroendocrine, vascular, neurological, and muscle systems contribute as physiological determinants of the muscle weakness. Complex and multifaceted biological mechanisms drive the post-ICU muscle dysfunction with mitochondrial and autophagy dysfunction, epigenetic modifications, cellular senescence, muscle inflammation with altered cell–cell communication, including dysfunction of immune cells, stem cell exhaustion and extracellular matrix remodelling. The review also sheds light on new and innovative therapeutic approaches and discusses future research directions. Emphasis is placed on the potential for multi-approach treatments that integrate nutritional, physical, and biological interventions. Addressing these aspects in a holistic and dynamic manner, from ICU to post-ICU phases, may provide avenues for mitigating the long-term burden of muscle weakness and physical disability in ICU survivors.

 

Post-extubation dysphagia in the ICU−a narrative review: epidemiology, mechanisms and clinical management (Update 2025)

Critical Care volume 29, Article number: 244 (2025) 

Abstract

Dysphagia (i.e. an impairment in swallowing function that impacts on safety or efficiency) is present in many intensive care unit (ICU) survivors, in particular following extubation (“post-extubation dysphagia”, PED). Despite the fact that pathomechanisms leading to PED are currently incompletely understood, local as well as central neurological and neuromuscular dysfunctions may be key to development of PED. Data from prospective large-scale clinical investigations with systematic screening demonstrate that PED affects about one out of five (about 20%) of mixed medical-surgical unplanned (emergency) ICU admissions. PED is associated with an increased risk for aspiration, aspiration-induced pneumonia, malnutrition, increased ICU resource use, decreased quality of life, prolonged ICU- and hospital length of stay and increased overall morbidity and mortality. Data demonstrate that PED is an independent predictor of 90-day mortality with increased risk of death up to about one year after ICU admission. PED may be a somewhat overlooked medical problem since in many ICUs, PED is currently not routinely screened for in all patients at risk (i.e. all ICU patients) following extubation. In this review, we update the available data on PED with a focus on epidemiology, risk factors, potential aetiology and treatment approaches, as well as clinical management on ICUs.

 

Decoding portal vein pulsatility: hemodynamic determinants in a post-hoc analysis of a prospective observational trial

Annals of Intensive Care volume 15, Article number: 81 (2025) 

Background

The portal vein pulsatility index (PVPI) reflects systemic congestion and is influenced by both volume status and right ventricular (RV) function. The mean systemic filling pressure analogue (Pmsa), derived from a mathematical model, estimates the interaction between stressed blood volume and systemic vascular compliance, serving as surrogate marker of volume status. This post-hoc analysis of an observational trial investigates the combined role of Pmsa and RV function as determinants of PVPI using echocardiography. Fifty-five mechanically ventilated patients with circulatory failure were included within 6 h of ICU admission following elective open-heart surgery. Fluid-tolerant patients (PVPI < 50%) underwent a passive leg raising (PLR) test; fluid-responsive patients subsequently received 7 mL/kg of Ringer’s lactate. PVPI and Pmsa were measured at five timepoints: baseline (T1), after PLR (T2), upon returning to baseline (T3), after fluid administration (T4), and 20 min post-infusion (T5). RV function parameters, including RV to LV end-diastolic area ratio (RVEDA/LVEDA), tricuspid lateral annular systolic velocity (RV S’), RV fractional area change (RVFAC), pulmonary acceleration time (PAT), and right myocardial performance index (RIMP)—were assessed at T1, T4, and T5. Only fluid-responsive patients were evaluated beyond T3.

Results

At T1, robust multilinear regression including all patients identified RVEDA/LVEDA (β = 10.38; p < 0.001), RIMP (β = − 6.54; p = 0.002), and RV S’ (β = − 0.60; p = 0.002) as significant determinants of squared PVPI. In all patients, repeated measures correlation between Pmsa and PVPI was strong across T1-to-T3 (ρ = 0.785; p < 0.001), increasing from a non-significant correlation at T1 (ρ = 0.215; p = 0.115). Generalized estimating equations conducted only in fluid-responsive patients across T1, T4, and T5 identified Pmsa (β = 4.19; p < 0.001), RV S’ (β = − 5.84; p < 0.001), RVEDA/LVEDA (β = 34.85; p = 0.018), and RIMP (β = − 35.28; p = 0.039) as significant determinants of PVPI.

Conclusion

RV function and Pmsa are key determinants of PVPI. Their combined assessment may support an individualized congestion management by guiding interventions toward volume status, RV function, or both.

 

Sodium bicarbonate administration for metabolic acidosis in the intensive care unit: a target trial emulation

Intensive Care Medicine

Published: 10 June 2025, Volume 51, pages 1–9, (2025)

Purpose

Sodium bicarbonate is commonly administered to treat metabolic acidosis in intensive care units (ICUs). There is limited evidence from randomized trials to support this practice, and observational studies show conflicting results. Our aim was to perform a target trial emulation evaluating the effect of bicarbonate therapy on mortality.

Methods

Retrospective cohort study using data from 12 Australian ICUs. Inclusion criteria were adults with pH < 7.3 and PCO₂ ≤ 45 mmHg within the first three days. We excluded repeat admissions, toxicology, diabetic ketoacidosis, and pre-existing end-stage renal failure. The treatment intervention was sodium-bicarbonate administration, and the primary outcome was 30-day ICU mortality with ICU discharge as a competing event. We evaluated multiple subgroups, including patients with acute kidney injury, requirement for vasoactive therapy, and pH < 7.2. The primary model utilized a parametric g-computation and rolling entry matching was performed as a sensitivity analysis.

Results

We identified 6157 eligible admissions, of which 1764 (29%) received sodium bicarbonate. Bicarbonate therapy was associated with a 1.9% absolute mortality reduction for the primary analysis [risk ratio 0.86, 95% confidence interval (CI) 0.80 to 0.91], and significant benefits were seen across all subgroups evaluated. A similar point estimate of 2.1% was observed in the sensitivity analysis, with a sustained mortality reduction seen at 30 days.

Conclusion

In this target trial emulation, bicarbonate administration was associated with a small but statistically significant reduction in mortality for patients with metabolic acidosis. Large sample sizes would be required to demonstrate this effect in a randomized trial.

Critical Care Bulletin - May 2025

 

Endotoxin hemoadsorption in refractory septic shock with multiorgan dysfunction and extreme endotoxin activity

Critical Care volume 29, Article number: 206 Published: 20 May 2025

Abstract

Endotoxin septic shock is marked by severe organ failure and mortality rate that exceeds fifty percent, underscoring the critical need to tailor management strategies. Monitoring -endotoxin activity can guide the initiation and direction of adjunctive treatment for refractory septic shock through hemoadsorption. Thus, intervening based on the pathophysiological foundation may potentially improve outcomes. This represents a step towards precision medicine in the management of septic shock adjunctive therapies, addressing a knowledge gap in this pathology that remains insufficiently defined. Despite its potential, in the setting of refractory septic shock and multiorgan dysfunction with extreme endotoxin activity (EAA ≥ 0.9), the data about efficacy of endotoxin hemoadsorption is scarce.